Search Results (277)

The keeping of companion chicken flocks has recently grown in popularity, increasing the demand for advanced veterinary care. The clinical utility of echocardiography is currently limited by a lack of established reference intervals for adult chickens of non-commercial breeds. Therefore, the objective of this prospective observational study was to establish echocardiographic reference intervals for adult chickens of non-commercial breeds. Healthy adult chickens (n = 126) of both sexes and various breeds were administered intramuscular butorphanol (2 mg/kg) and midazolam (2 mg/kg) before undergoing echocardiography by a board-certified veterinary cardiologist. Using nonparametric methods, 95% reference intervals were determined, with the 2.5th (90% CI) and 97.5th (90% CI) percentiles serving as the lower and upper limits, respectively. The effect of body weight on linear cardiac dimensions was evaluated by regression analysis, and allometric equations scaled to body weight were derived for each variable. Intraclass correlation coefficients were used to quantify echocardiographic intra- and interoperator repeatability and intra- and interobserver measurement agreement. Body weight was a significant but not strongly correlative co-variate, and 95% prediction intervals for linear dimensions were determined by allometric scaling. Echocardiographic reference intervals were established from 126 chickens of non-commercial breeds. Full article

Although radiotherapy is a cornerstone in the management of several pediatric malignancies, its administration in children poses unique anesthetic challenges. Unlike adults, pediatric patients, particularly younger children, often require repeated sedation or general anesthesia to ensure immobility and reduce psychological distress during daily treatment sessions that may extend over several weeks. This narrative review summarizes current evidence on anesthetic strategies for children undergoing radiotherapy, focusing on clinical indications, pharmacological approaches, safety considerations, and organizational aspects. We discuss the main sedation and anesthesia techniques used in non-operating room anesthesia (NORA) settings, including deep sedation with midazolam, propofol, ketamine, and dexmedetomidine, as well as general anesthesia with laryngeal mask airway management. Particular attention is given to the cumulative effects of repeated anesthetic exposure, airway management challenges in remote radiation environments, and the risk of respiratory and hemodynamic complications. The review also highlights the importance of individualized, protocol-driven management, rapid recovery strategies, and continuous remote monitoring systems. Non-pharmacological interventions and audiovisual-assisted techniques are also discussed as potential strategies to reduce anesthesia requirements in selected patients. A multidisciplinary approach involving anesthesiologists, radiation oncologists, nurses, psychologists, and technical staff is essential to optimize safety, treatment adherence, and overall quality of care. Tailored anesthetic management, supported by standardized protocols and specialized pediatric expertise, remains crucial to balancing procedural efficacy with short- and long-term safety in this vulnerable population. Full article

Background: Delirium is a frequent and serious complication in intensive care units (ICUs), associated with increased mortality, prolonged mechanical ventilation, extended length of stay, and long-term cognitive impairment. This study aimed to assess ICU nurses’ knowledge and practices regarding delirium management in Cyprus and to identify predictors of knowledge. Methods: A cross-sectional study was conducted among nurses working in adult ICUs in Cyprus. Data were collected using a structured self-administered questionnaire that included demographic characteristics, sedation and analgesia practices, and an adapted Delirium Knowledge Questionnaire incorporating ICU-specific items. Results: A total of 70 ICU nurses participated, most of whom were female (60%) with a mean ICU experience of 5.1 years. Only 27.1% reported daily delirium screening, although 65.2% perceived delirium as frequent. Sedation protocols were reported by 34.3%, sedation scales were used by 44.3%, and daily sedation interruption by 61.4%. Only 15.7% had received formal delirium training, while 87.1% expressed the need for further education. Knowledge scores were moderate to high (68.5–84.0%), with higher scores among nurses with prior training and female nurses (p = 0.003). Hospital type was associated with sedation practices, with greater use of sedation scales in public ICUs (p < 0.001) and propofol more commonly used as first-line sedation compared with midazolam in private ICUs (p = 0.018). Conclusions: Although ICU nurses demonstrated moderate knowledge of delirium, systematic screening and protocolized management remain suboptimal. Structured education and standardized implementation strategies are required to strengthen patient safety in critical care settings. Full article

Background and Objectives: One of the two primary classes of drugs administered in ICUs for pharmacological sedation is benzodiazepines. Among these, anesthesiologists consider midazolam the most commonly used and clinically significant agent. Materials and Methods: A prospective, single-center investigation involving 25 patients was carried out in the ICU. The study population consisted of patients undergoing mechanical ventilation with an FiO₂ exceeding 60%, as well as ventilated individuals requiring additional support such as ECMO, NO, or ECCOR over 24 h before the study. Participants under 18 years of age or those not receiving continuous midazolam infusion were excluded. Measurements obtained from RASS and BIS were then compared with serum midazolam concentrations. On each day, when blood samples for midazolam measurements were taken, additional laboratory tests assessing renal and hepatic function were also carried out. Results: A negative correlation was shown between RASS and midazolam dosage (r = −0.44, p < 0.001), midazolam concentration (r = −0.33, p < 0.001), and α-OH-midazolam concentration (r = −0.24, p = 0.008). Similarly, a negative correlation was shown between BIS and midazolam concentration (r = −0.3, p = 0.016), as well as α-OH-midazolam (r = −0.3, p = 0.016). We observed that deceased patients received higher doses of midazolam to maintain the minimum level of required sedation compared to the others (135.5 ± 75.1 mg vs. 39.6 ± 59.2 mg; p = 0.002), indicating that these patients had higher concentrations of both midazolam and α-OH-midazolam (148.6 ± 83.5 µg/L vs. 27.2 ± 36.1 µg/L; p < 0.001, and 18 ± 15.9 vs. 5.3 ± 6.1 µg/L; p < 0.001). Conclusions: The results show that routine monitoring of midazolam does not provide additional clinical value. However, further studies are needed in high-risk groups. Despite the high mortality rate in the ICU for patients with severe respiratory failure, the six-month survival rate for discharged patients was high, exceeding 80%. Full article

Objectives: The co-administration of Bruton’s tyrosine kinase (BTK) inhibitors with antiretroviral drugs is challenging due to potential drug–drug interactions (DDIs). However, clinical trials specifically assessing such DDIs are lacking. We aimed to evaluate DDIs between the BTK inhibitors ibrutinib, zanubrutinib and acalabrutinib with representative antiretroviral drugs and to provide dose adjustment strategies using physiologically based pharmacokinetic (PBPK) models. Methods: PBPK models were developed in PK-Sim software. Model performance was verified by comparing simulated pharmacokinetic parameters and DDI magnitudes with probe drugs (midazolam or maraviroc) with reported clinical data. The validated models were subsequently applied to assess DDIs and explore dose adjustment strategies. Results: The developed PBPK model accurately describes the pharmacokinetics of each drug. Darunavir/ritonavir substantially increased the maximum plasma concentration (C_max) of ibrutinib, zanubrutinib, and acalabrutinib by 496%, 312%, and 160%, respectively. In contrast, efavirenz reduced C_max by 43%, 33%, and 37%, respectively, while etravirine caused smaller decreases of 5%, 0%, and 10%. Based on these predictions, recommended dose adjustment strategies include ibrutinib 105 mg once daily, zanubrutinib 40 mg twice daily, and acalabrutinib 50 mg twice daily when co-administered with darunavir/ritonavir or ibrutinib 980 mg once daily, zanubrutinib 240 mg twice daily, and acalabrutinib 150 mg twice daily when co-administered with efavirenz. No dose adjustment is required with etravirine. Conclusions: The PBPK models accurately predicted the in vivo pharmacokinetics of ibrutinib, zanubrutinib, acalabrutinib, and those of the antiretrovirals darunavir/ritonavir, efavirenz, and etravirine, and the DDIs between them. The dose adjustment strategies provided information valuable to the optimization of antineoplastic therapy in HIV-related lymphoma (HRL) patients. Full article

Background and Objectives: Gastrointestinal (GI) endoscopy requires safe and effective sedation. Remimazolam, an ultra-short-acting benzodiazepine, may offer advantages over traditional sedatives like midazolam and propofol, including rapid onset, short half-life, and a favorable safety profile. This study evaluates the feasibility, safety, and patient satisfaction of continuous remimazolam infusion administered by trained gastroenterologists for GI endoscopy. Materials and Methods: This prospective registry included patients with ASA physical status I and II undergoing standard endoscopic procedures. Continuous remimazolam sedation was administered, with boluses given as needed. Vital signs were monitored, and patient satisfaction was assessed before and after the procedure using standardized questionnaires. Results: A total of 159 procedures were performed in 141 patients. Sedation was successful in all patients, with a mean induction dose of 7.1 mg and total infusion of 15.1 mg. Recovery time averaged 3.3 min. Adverse events, including transient hypotension and hypoxia, occurred in 11.3% of patients but were easily managed. Most patients (97%) reported sufficient comfort, with an average satisfaction score of 8.1/10. Conclusions: Continuous remimazolam infusion administered by trained gastroenterologists is a safe and effective alternative to traditional propofol sedation for GI endoscopy. It offers stable sedation, rapid recovery and high patient satisfaction, potentially reducing anesthesiology workload and improving procedural efficiency. Further studies are needed to confirm these findings in broader patient populations. Full article

Background/Objectives: An 8-kg, 16-month-old child was brought to the emergency department of a regional community hospital with shallow respirations. Due to her pallor and the diluted appearance of the first blood sample, the emergency physician suspected sepsis associated with severe anemia. Her first laboratory results revealed a hemoglobin of 1.7 g/dL. Subsequent laboratory data revealed positive fibrin split products and hypofibrinogenemia with reticulocytosis. Because this regional community hospital did not have a pediatric intensivist, the emergency physician instead consulted a neonatal intensivist for guidance. Methods: A femoral intraosseous line was placed to allow aggressive massive transfusion. After consultation with the neonatal intensivist, packed red blood cells were transfused at a rate of 30 mL/kg/h. After transfusion, the patient became agitated and required repeated paralytic, sedative, and analgesic boluses of succinylcholine, ketamine, midazolam, dexmedetomidine, and fentanyl, with fentanyl and dexmedetomidine drips. The patient arrived at a tertiary care center 13 h after admission. Results: At the tertiary care center, the patient was weaned off the drips and was theorized to have secondary autoimmune hemolytic anemia due to sepsis after positive direct and indirect Coombs test. She was treated with a course of antibiotics, including cefepime and vancomycin, without steroids or immunotherapy. Five months later, her hemoglobin had returned to 12.1 g/dL, and she tested negative on direct and indirect Coombs test. Conclusions: This case highlights the importance of collaboration between and within departments to successfully manage pediatric hemostatic resuscitation. Full article

Background: Hypersensitivity reactions to benzodiazepines, although uncommon, represent a clinically relevant issue in perioperative practice. Benzodiazepines are widely used medications with anxiolytic, sedative, and anticonvulsant properties. The objective of this review is to synthesize current knowledge on benzodiazepine hypersensitivity, focusing on underlying mechanisms, clinical manifestations, diagnostic considerations, and strategies for management and prevention in the perioperative setting. Methodology: A narrative synthesis of the current literature on hypersensitivity reactions to benzodiazepines was performed. The review included published case reports, case series, and clinical studies describing hypersensitivity reactions, their clinical presentation, and diagnostic approaches. Particular attention was given to both immunological and non-immunological mechanisms, reported clinical phenotypes, and issues relevant to perioperative patient safety. Results: The extant evidence suggests that benzodiazepine hypersensitivity may involve both immunological and non-immunological pathways. The spectrum of reported reactions encompasses mild cutaneous manifestations and severe systemic responses, although the incidence remains low. This review highlights diagnostic challenges related to variable clinical presentation and the limited availability of standardized testing methods. Conclusions: Although cases of benzodiazepine hypersensitivity are uncommon, awareness of potential reactions is critical for ensuring safe clinical practice. This review emphasizes the necessity for additional research to elucidate the underlying mechanisms, standardize the diagnostic criteria, and formulate management protocols. Full article

Background: Ribociclib, initially approved for HR+/HER2− advanced breast cancer (ABC) at a 600 mg dose, was recently approved for HR+/HER2− early breast cancer (EBC) at a 400 mg dose based on the NATALEE trial. Differences in dose and patient population warrant reassessment of ribociclib drug–drug interactions (DDIs) and the impact of hepatic or renal impairment (HI/RI) in EBC patients to guide co-medication management and subpopulation dose recommendations. Methods: Physiologically-based pharmacokinetic (PBPK) modeling based on a healthy volunteer population was conducted to assess ribociclib DDIs with CYP3A4 substrates/modulators in patients with EBC. Subgroup analysis from NATALEE assessed HI/RI impact on ribociclib PK in EBC patients. Existing data from ABC/advanced cancer patients and non-cancer subjects were also integrated to inform dose recommendations for EBC subpopulations. Results: PBPK modeling predicted that ritonavir or erythromycin (strong and moderate CYP3A4 inhibitors) would increase ribociclib steady-state area under the concentration–time curve (AUC) by 1.84-fold or show no meaningful impact, respectively. Steady-state ribociclib AUC was estimated to decrease by 83% and 74% with rifampicin and efavirenz, strong and moderate CYP3A4 inducers, respectively. Ribociclib was estimated to increase CYP3A4 substrate midazolam exposure by 280%. Mild HI or mild/moderate RI did not show an apparent impact on ribociclib PK. Conclusions: Using relevant data and methodology for EBC patients, this analysis informed the approved ribociclib label of no dose adjustment for EBC patients with concomitant use of a moderate CYP3A inhibitor, any degree of HI, or mild/moderate RI, and a reduced 200 mg dose for patients with concomitant use of a strong CYP3A inhibitor or severe RI. Full article

Background/Objectives: Insulin and glucagon are key hormones in metabolic regulation. There are limited comparative data on how common rodent anesthetic regimens influence hormone secretion, leading to misinterpretation of results. We aimed to compare the effects of several anesthetic regimens on insulin and glucagon secretion using the physiologically relevant isolated perfused rat pancreas model. Methods: Six commonly used rodent anesthetic regimens were assessed for their ability to induce surgical depth of anesthesia. Once achieved, the pancreas was vascularly isolated and perfused. After euthanasia, the pancreas was stimulated with glucose and glucagon-like peptide-1 (GLP-1). Insulin and glucagon were measured in the effluent using radioimmunoassay. Results: Anesthesia with Hypnorm^® (fentanyl/fluanisone)/midazolam produced the most physiological responses, meaning that insulin was secreted in response to hyperglycemia and GLP-1, and glucagon was secreted under hypoglycemia. Ketamine/dexmedetomidine anesthesia abolished insulin dynamic secretion and blunted glucagon secretion. Isoflurane/buprenorphine anesthesia partially suppressed insulin secretion, but it still followed a physiological pattern in response to glucose fluctuations. However, it abolished the dynamic glucagon responses to glucose. Three additional anesthetic regimens failed to produce surgical depth anesthesia and were therefore not further analyzed. Conclusions: Different anesthetic regimens altered pancreatic hormone secretion. Fentanyl/fluanisone/midazolam was associated with dynamic insulin and glucagon secretion, whereas ketamine/dexmedetomidine and isoflurane/buprenorphine altered the pattern and/or magnitude of hormone secretion. Overall, the choice of anesthesia is a critical variable in animal experimentation for metabolic studies and may confound the interpretation of results. Full article

Background: Dental fear and anxiety are highly prevalent in children, resulting in avoidance or incomplete dental treatment; sedation emerges as a possible behavioral management strategy. This umbrella review aimed to provide a structured and critical synthesis of the available knowledge on sedative single-agent efficacy and routes of administration employed for achieving sedation (excluding deep sedation/general anesthesia) during dental procedures in children for behavior management, as well as to evaluate acceptability and satisfaction for child, caregiver, and provider, and to assess the influence of clinical setting and provider. Methods: In line with the PRISMA statement, the protocol was registered on PROSPERO (CRD420251043738), and 18 systematic reviews were included and synthesized qualitatively. Results: Single-agent sedation was safe and effective for managing behavior in children during dental procedures, with midazolam and nitrous oxide being the most studied agents. Different routes of administration showed distinct characteristics in onset, recovery time, adverse effects and cooperation, while agent selection appeared influenced by clinical setting and provider type. However, data on acceptability and satisfaction from children, caregivers, and providers remains limited. Conclusions: Evidence suggests potential effectiveness of selected agents and routes in appropriately monitored settings, but data heterogeneity precludes strong comparative recommendations. Further studies are therefore needed to address the existing gaps in pediatric dental sedation. Full article

Introduction: Postoperative delirium, including emergence agitation, is recognized in the post-anesthesia care unit as a fluctuating disturbance of attention and cognition. The current evidence examined suggests that both anesthetic agents and postoperative pain intensity may influence the risk of delirium. The aim of this review is to discuss the significance of pharmacological agents used during anesthesia and the relationship between the intensity of postoperative pain and the occurrence of postoperative delirium in patients undergoing surgical procedures, regardless of age. Methods: A scoping review was conducted from December 2024 to December 2025. The articles identified in each search were limited to those published between 2015 and 2025. Results: Agents such as dexmedetomidine, remimazolam, and magnesium sulfate were examined in the included trials and were reported to be associated with reducing the incidence and severity of postoperative delirium, particularly in pediatric and elderly patients. Analysis of clinical trial outcomes conducted in pediatric populations undergoing various surgical procedures suggests that dexmedetomidine (administered intranasally and intravenously) and alfentanil were associated with lower incidence and severity of emergence delirium compared to standard care or other agents (e.g., midazolam). Higher doses of dexmedetomidine (2 µg/kg) were reported to be associated with improved postoperative analgesia and reduced agitation, without prolonging recovery time or causing serious adverse effects. Propofol, due to its rapid metabolism, was suggested to contribute to shorter emergence times; however, its impact on cognitive function requires further investigation. Additionally, there remains a lack of agreed-upon and/or validated tools and strategies for pain assessment in patients experiencing delirium. Conclusions: The current evidence examined suggests that the use of intranasal dexmedetomidine at appropriate doses may be associated with reduced postoperative pain and agitation without prolonging recovery time or increasing the risk of serious adverse events. Hydromorphone was reported in the included trials to be associated with better postoperative pain control than sufentanil, whereas remimazolam, although associated with reduced delirium incidence in some trials, did not influence the length of stay in the post-anesthesia care unit. Magnesium sulfate, although not significantly affecting the incidence of delirium, was associated with alleviation of postoperative symptoms such as pain and insomnia in adult patients. Ketamine, while commonly used for analgesic therapy, did not demonstrate a consistent association with delirium prevention and, in some studies, was associated with increased neuropsychiatric events. Further research is required to more precisely define optimal perioperative delirium prevention protocols. Full article

Seizure clusters (SCs) are an acute and transient increase in seizure frequency relative to an individual patient’s baseline and are associated with an increased risk of injury, morbidity, and potentially mortality if not promptly and adequately treated. Despite their clinical importance, the management of SCs remains highly heterogeneous, primarily due to the absence of a universally accepted definition, which is determined also by the wide variability in seizure semiology and baseline individual burden;, as well as by differences in care settings. Outpatient treatment relies largely on caregivers’ ability to recognize SCs and administer rescue medication, whereas inpatient management may also involve invasive routes of administration. We conducted a literature review identifying 32 original articles addressing the treatment of SCs. The analysis focused on definitions, efficacy outcomes, and adverse events across three clinical scenarios: outpatient, Emergency Department (EDs) and Epilepsy Monitoring Units. The results show that in the outpatient setting, the available evidence suggests that diazepam nasal spray (DZP-NS), midazolam nasal spray (MDZ-NS), and oral lorazepam (LZP) solution may demonstrate comparable efficacy and safety. However, comparisons are limited by heterogeneity in studies’ designs, patient populations and outcome definitions, as well as by the absence of head-to-head trials. Moreover, geographic differences in drug availability (e.g., USA vs. Europe) limit the development of universally applicable treatment protocols. Consequently, the off-label use of oral benzodiazepines, including clobazam, clonazepam, and lorazepam, remains common when oral therapy is feasible, despite limited evidence. The implementation of a patient-specific Acute Seizure Action Plan (ASAP) incorporating an individualized SC definition is recommended. In contrast, inpatient management shows greater consensus, largely reflecting first-line treatment paradigms for status epilepticus. These include prompt intravenous benzodiazepine administration, followed by the intravenous loading of antiseizure medications such as brivaracetam or lacosamide in cases of seizure recurrence. In ED settings, “empirical” definitions of SCs (i.e., more than three seizures within 24 h) may facilitate timely intervention. Full article

Remimazolam is an ultra-short-acting benzodiazepine developed according to the “soft drug” concept and characterized by rapid onset, predictable offset, organ-independent metabolism, and the availability of a specific antagonist. Due to these pharmacological features, this drug represents a particularly attractive option for pediatric anesthesia and sedation, a field in which traditional agents are often limited by hemodynamic instability, prolonged recovery, and adverse respiratory effects. This narrative review summarizes and discusses the current evidence regarding the use of remimazolam in pediatric patients, focusing on pharmacokinetics, pharmacodynamics, clinical applications, and safety. Available data indicate that remimazolam provides effective sedation and anesthesia in children across multiple settings, including induction of general anesthesia, non-operating room anesthesia, and intensive care unit sedation. Compared with propofol and midazolam, remimazolam is generally associated with greater hemodynamic stability, rapid recovery, reduced emergence delirium, and a favorable respiratory profile, while maintaining comparable efficacy. Intranasal administration has also shown promise as a premedication strategy for reducing preoperative anxiety, although it may occasionally be associated with pain. Even if remimazolam lacks intrinsic analgesic properties, its use appears to indirectly improve postoperative comfort by attenuating stress responses and emergence agitation. Despite encouraging results, pediatric use of remimazolam remains off-label in many countries, and evidence is still limited by small sample sizes and heterogeneous protocols. Further large-scale randomized controlled trials are needed to define optimal dosing strategies, long-term safety, and their definitive role in pediatric anesthetic and sedative practice. Full article

Background: Rapid Sequence Induction (RSI) is a widely used method for emergency airway management in critically ill and clinically unstable patients. Beyond the risks inherent to the procedure itself, RSI is almost exclusively performed in emergency settings where patients present with severe physiological derangement and a high risk of aspiration. In postmortem examinations, forensic toxicology results may be influenced by the patient’s clinical condition, the sampling site, the postmortem interval (PMI), and postmortem drug redistribution (PMR). This review aims to evaluate the existing literature regarding PMR of drugs commonly used during RSI. Methods: PubMed/MEDLINE, Embase and the Cochrane Library were searched for studies on PMR of drugs used in intravenous (IV) RSI (up to November 2025). Human and animal studies, patient populations comparable to critically ill individuals requiring RSI, and forensic case reports of exclusively IV drug administration were included. Studies on recreational use, overdose and non-IV administration were excluded. Results: Data on the PMR of IV-administered RSI drugs remain limited. Most available studies involve Intensive Care Unit (ICU) patients or individuals who underwent RSI in emergency settings. Fentanyl and midazolam appear to demonstrate notable PMR. Several factors influencing postmortem drug concentrations were identified. Although these findings are consistent with the existing literature, the small number of studies and the heterogeneity of data preclude definitive conclusions. Conclusions: Critical patient condition, including frailty due to advanced age, hemodynamic instability (particularly in ICU patients), hypoalbuminemia, body mass index (BMI), and injury and/or trauma, as well as the interval between IV drug administration and death, appear to affect postmortem concentrations of drugs used during RSI. The potential for PMR of certain agents, such as fentanyl and midazolam, adds further complexity. Given the scarcity of consolidated evidence and until further research provides more robust data, postmortem drug levels should not be interpreted as directly reflective of antemortem concentrations. Full article